Clinical Lecturer Auburn University Auburn, AL, United States
Background In humans, omeprazole-induced gastric pH increase interferes with absorption of co-administered oral drugs. Despite frequent co-administration in horses, its effect on flunixin meglumine absorption remains uninvestigated. Hypothesis/Objectives The study aimed to compare flunixin pharmacokinetics in adult horses with and without 5-day omeprazole treatment. We hypothesized that: I) omeprazole would increase gastric pH and reduce flunixin bioavailability; II) despite reduced bioavailability, flunixin would reach therapeutic plasma concentrations (>0.75 µg/ml). Animals Six healthy adult geldings from a research herd Methods Using a Latin-square crossover design, horses received flunixin (1.1 mg/kg) via intravenous (IV) route, intragastric (IG) route, and intragastric route after 5 days of 4mg/kg oral omeprazole (OM). Gastric pH was measured 24 hours before flunixin administration in IG and OM protocols using a pH meter (pH700, Oaklon®). Plasma flunixin concentrations were quantified by High Performance Liquid Chromatography at 14 time points over 36 hours and analyzed via non-compartmental pharmacokinetics (Excel PKSolver®). Gastric pH and pharmacokinetic variables were compared between IG and OM protocols using paired t-tests (p< 0.05). Results In the OM protocol, gastric pH was alkaline in all horses (7.61±0.42) and significantly higher (p=0.0001) than in the IG protocol (2.99 ±1.34). Flunixin plasma concentration versus time data are reported in figure 1. Omeprazole significantly reduced flunixin bioavailability, maximum concentration, and overall drug exposure (table 1). Conclusions and Clinical Importance Omeprazole-induced gastric pH elevation significantly reduced flunixin absorption but did not prevent plasma concentrations from reaching therapeutic levels for clinically relevant durations.
